HBV (Hepatitis B Virus) has seriously endangered human health, causing huge economic and mental burdens to patients and their families, and has also created enormous labor and economic losses and even social problems such as serious employment. The goal of chronic hepatitis B treatment is to inhibit HBV replication before significant liver damage occurs. Currently, the international clinical guidelines for anti-HBV drugs include interferon (IFN) and nucleoside analogues, which are immune regulator and HBV DNA polymerase inhibitor, respectively. Both drugs have some effects, but also have shortcomings. INF has severe side effects, and most patients cannot tolerate. Nucleoside analogues require long-term use, and their long-term safety is unknown. In addition, nucleoside analogues cannot effectively eliminate HBV cccDNA (covalently closed circular DNA). There is drug resistance and relapse. Thus, existing antiviral drugs have some defects, so the complete clearance of HBV and cure caused by chronic Hepatitis B is still difficult to achieve. In the process of HBV replication, nucleotides play a very important role as a raw material for the synthesis and replication of HBV DNA, and the sugar metabolites intermediate ribose-5-phosphate is the raw material of nucleotides, so the glucose metabolism process is involved in the HBV DNA synthesis and replication process. AKT is a key regulatory factor in the process of glucose metabolism.
AKT (i.e., protein kinase B or PKB), which was originally thought to be isolated from AKR murine T-cell lymphoma in 1987, is a human homologue of the retrovirus AKT8 virus oncogene. The structure of AKT includes a PH site, a central kinase site and a hydrophobic HM regulatory site at the amino terminus, and the main phosphorylation sites are T308 and S473. AKT plays an important role in cell survival, growth, migration, migration, polarity, metabolism, cell cycle progression, skeletal muscle and myocardial contractility, angiogenesis, and stem cell self-renewal. mTOR (mammalian target of rapamycin) protein is a family member of phosphoinositide 3 kinase-related kinase, which integrates various extracellular signals such as nutrition, energy and growth factor, participates in biological processes such as gene transcription, protein translation and ribosome synthesis, and plays an important role in cell growth and apoptosis. mTOR has two complex forms, namely mTORC1 (mTOR complex 1) and mTORC2. mTOR is a downstream protein of AKT. After activation of AKT, it phosphorylates TSC2 and inhibits the formation of TSC½ complex, thus releasing the inhibition of Rheb and activating mTORC1. At the same time, AKT can directly phosphorylate PRAS40, thereby reducing the negative regulation of PRAS40 in mTORC1, and enhancing the activity of mTORC1. mTORC2 complex activates AKT by phosphorylation of the AKT-s473 site. Recent study indicates that these two proteins can lead to various diseases such as cancer, diabetes, cardiovascular disease, inflammatory diseases, fibrotic diseases, pulmonary hypertension, aging, neurodegenerative diseases, epilepsy, mental retardation, autism, but there are few reports of AKT and mTOR related to HBV.